Etiology of cervical cancer is associated with excessive inflammation mediated tumorigenesis. Pro and anti-inflammatory cytokines (tumor necrosis factor alpha, TNFA and interleukin, IL-10) are involved in fighting against the tumorigenesis. Therefore, the present study was designed to evaluate the association of TNFA (-308G>A) and IL-10 (-819C>T) gene polymorphism with risk of cervical cancer. One hundred fifty histopathologically confirmed patients with cervical cancer and 162 age, ethnically-matched cervical cytology negative healthy controls were genotyped for TNFA (-308 G>A) and IL-10 (-819 C>T) polymorphisms using PCR-RFLP. Individuals with combination of TNFA -308GA+AA genotype and A allele were at elevated risk of cervical cancer (odds ratio (OR) = 2.24; P = 0.018 and OR, 2.05; P = 0.012). Frequency of IL-10 -819CT+TT genotype combination and T allele was slightly higher in cases as compared with controls but difference was not significant (OR = 1.52; P = 0.069 and OR = 1.38; P = 0.051). In association of genotypes with clinical characteristics, presence of TNFA -308GA+AA genotype conferred high risk for the stages (IB) (OR = 2.86, P = 0.039) and stages (III) (OR = 2.52; P = 0.015) of cervical cancer. In contrast, IL-10 -819TT genotype was not associated with higher risk of clinical characteristics of cervical cancer. In conclusion, individuals with TNFA -308*A allele carriers were at significantly higher risk of cervical cancer particularly early (IB) and advanced stages (III). However, IL-10 (-819C>T) polymorphism was not associated with risk of cervical cancer.

No abstract

Most polyphenols can cross blood-brain barrier, therefore, they are widely utilized in the treatment of various neurodegenerative diseases (ND). Resveratrol, a natural polyphenol contained in blueberry, grapes, mulberry, etc., is well documented to exhibit potent neuroprotective activity against different ND by mitochondria modulation approach. Mitochondrial function impairment is the most common etiology and pathological process in various neurodegenerative disorders, viz. Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis. Nowadays these ND associated with mitochondrial dysfunction have become a major threat to public health as well as health care systems in terms of financial burden. Currently available therapies for ND are limited to symptomatic cures and have inevitable toxic effects. Therefore, there is a strict requirement for a safe and highly effective drug treatment developed from natural compounds. The current review provides updated information about the potential of resveratrol to target mitochondria in the treatment of ND.

No abstract

Inflammation plays a major role in the pathogenesis of cervical cancer. Chemokines are involved in inflammation, cancer, and infectious diseases. Therefore, we evaluated the association of the chemokine receptor gene polymorphism CCR5 Delta32 with risk of cervical cancer. A total of 150 histopathologically confirmed patients with cervical cancer and 162 age and ethnically matched cervical cytology negative healthy controls were genotyped for CCR5 Delta32 polymorphisms using PCR. Association of CCR5 Delta32 genotypes with risk of cervical cancer, clinical stages, and tobacco exposure was analyzed using chi-square statistical tests. The frequency of the mutant allele CCR5 Delta32 was higher in patients with cervical carcinoma (2.3%) but there was no statistically significant difference (OR = 1.51; p = 0.685;). Association of CCR5 genotypes with clinical phenotypes showed significant risk with stage IB patients due to CCR5+/Delta32 genotype (OR = 4.43; p = 0.021). Furthermore, patients with CCR5+/Delta32 genotype and tobacco usage were at risk of cervical cancer (OR = 1.73, 95% CI = 0.27-1.28). In summary, CCR5 heterozygous genotype (+/Delta32) may significantly influence the early stage of cervical cancer development. However, the cervical cancer risk due to tobacco usage was not significantly modulated after interaction with CCR5+/Delta32 genotype.

Glutathione S-transferase (GST) family is involved in a two-stage detoxification process of a wide range of environmental toxins, carcinogen and antiretroviral (ARV) therapy (ART) drugs. The aim of this study is to describe the impact of genetic polymorphisms of GSTM1, GSTT1 and GSTP1-313A/G in the risk of ARV-associated hepatotoxicity in HIV-infected individuals and its modulation in hepatotoxic patients. We enrolled a total of 34 patients with hepatotoxicity, 131 HIV-infected individuals without hepatotoxicity under non-nucleoside reverse transcriptase inhibitor containing ART and 153 unrelated healthy individuals. With a case-control design, polymorphisms of GSTM1, GSTT1 and GSTP1-313A/G gene were genotyped by PCR and restriction enzyme-length polymorphism. Genotypes of GSTT1 null were significantly higher in HIV-infected individuals as compared with healthy controls (P=0.01, odds ratio (OR)=1.54). HIV-infected individuals with GSTM1-null genotype showed higher risk (P=0.09, OR=1.37) for hepatotoxicity, but risk was not significant. On evaluating gene-gene interaction models, GSTM1 null and GSTT1 null showed significant association with the risk of hepatotoxicity in HIV-infected individuals (P=0.004, OR=2.67) owing to synergistic effect of these genes. Individuals with GSTT1-null and GSTM1-null genotypes showed higher risk of hepatotoxicity with advanced stage of (CD4<200) of HIV infection (P=0.18, OR=1.39; P=0.63, OR=1.13). In case-only analysis, GSTT1-null genotype among alcohol users showed elevated risk of hepatotoxicity in HIV-infected individuals (P=0.12, OR=1.36, 95% confidence interval (CI): 0.94-1.97) as compared with GSTT1 genotypes. The carriers GSTM1-null+GSTT1-null genotype among nevirapine user showed prominent risk of hepatotoxicity in HIV-infected individuals (P=0.12, OR=4.21, 95% CI: 0.60-29.54). Hence, we can conclude that GSTT1-null and GSTM1-null genotypes alone and in combination may predict the acquisition of hepatotoxicity.

No abstract

The severity of hepatic injury depends upon cytokines. Previous studies associated IL-1RN allele 2 with IL-1β production. Hence, we examined the association of IL-1 RN and IL-1β polymorphisms with ARV-associated hepatotoxicity. Genotyping of IL-1RN (VNTR), IL-1β (-511C/T) polymorphisms was done in 162 HIV-infected patients, 34 with ARV hepatotoxicity, 128 without hepatotoxicity, and 152 healthy controls using PCR and PCR-RFLP method. The haplotypes 1T and 2C enhanced the risk for severe hepatotoxicity (OR = 1.41, P = 0.25; OR = 1.67, P = 0.31). IL-1β-511TT genotype significantly represented among tobacco using HIV-infected individuals compared to nonusers (OR = 3.74, P = 0.05). IL-1β-511TT genotype among alcohol users increased the risk for hepatotoxicity (OR = 1.80, P = 0.90). IL-1β-511CT and -511TT genotypes overrepresented in alcohol using HIV-infected individuals (OR = 2.29, P = 0.27; OR = 2.64, P = 0.19). IL-RN 2/2 and 1/3 genotypes represented higher in nevirapine using hepatotoxicity patients (OR = 1.42, P = 0.64, OR = 8.79, P = 0.09). IL-1β-511CT and -511 TT genotypes among nevirapine users enhanced the risk for severe hepatotoxicity (OR = 4.29, P = 0.20; OR = 1.95, P = 0.56). IL-1β-511CT and -511TT genotypes were overrepresented in combined nevirapine and alcohol using HIV-infected individuals as compared to nevirapine users and alcohol nonusers (OR = 2.56, P = 0.26; OR = 2.84, P = 0.24). IL-1β-511TT genotype with tobacco, alcohol, and nevirapine usage revealed a trend of risk for the development of ARV-associated hepatotoxicity and its severity.